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Updated: Jan 3, 2026
Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Short-term PM2.5 exposure induces sustained pulmonary fibrosis development during post-exposure period in rats
Baiyang Sun1, Yanfeng Shi1, Yang Li1
1Department of Toxicology and Sanitary Chemistry, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China.
Abstract:
Up to now, while some toxicological studies have identified pulmonary fibrosis immediately induced by long-term PM2.5 exposure, there has been no evidence indicating, whether short-term exposure can lead to post-exposure development of pulmonary fibrosis. Here, we treated rats with PM2.5 for 1 month (10 times), followed by normal feeding for 18 months. 18F-FDG intake, which is linked with the initiation and development of pulmonary fibrosis in living bodies, was found to gradually increase in lung following exposure through micro PET/CT imaging. Histolopathological examination revealed continuous deterioration of pulmonary injury post-exposure. Collagen deposition and hydroxyproline content continued to increase all along in the post-exposure duration, indicating pulmonary fibrosis development. Chronic and persistent induction of pulmonary inflammatory gene expression (Tnf, Il1b, Il6, Ccl2, and Icam1), epithelial mesenchymal transition (EMT, reduction of E-cadherin and elevation of fibronectin) and RelA/p65 upregulation, as well as serum inflammatory cytokine production, were also found in PM2.5-treated rats. Pulmonary oxidative stress, manifested by increase of MDA and decrease of GSH and SOD, was induced during exposure but disappeared in later post-exposure duration. These results suggested that short-term PM2.5 exposure could lead to sustained post-exposure pulmonary fibrosis development, which was mediated by oxidative-stress-initiated NF-κB/inflammation/EMT pathway.
Insights
Short-term exposure to fine particulate matter (PM2.5) can trigger long-term pulmonary fibrosis development in rats. This condition progresses even after exposure ceases, driven by inflammation and cellular changes.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Environmental Health
Background:
- Long-term PM2.5 exposure is linked to pulmonary fibrosis.
- The potential for short-term PM2.5 exposure to cause delayed pulmonary fibrosis remains unclear.
Purpose of the Study:
- To investigate if short-term PM2.5 exposure can induce post-exposure pulmonary fibrosis.
- To elucidate the underlying mechanisms of PM2.5-induced pulmonary fibrosis.
Main Methods:
- Rats were exposed to PM2.5 for one month, followed by an 18-month observation period.
- Micro PET/CT imaging, histopathological examination, and molecular analyses were employed.
- Assessed 18F-FDG uptake, collagen deposition, hydroxyproline content, inflammatory markers, epithelial-mesenchymal transition (EMT), and oxidative stress.
Main Results:
- PM2.5 exposure led to increased 18F-FDG uptake and progressive lung injury post-exposure.
- Histopathology confirmed continuous deterioration, increased collagen deposition, and hydroxyproline content.
- Chronic inflammation, EMT, NF-κB activation, and oxidative stress were observed, with oxidative stress resolving post-exposure.
Conclusions:
- Short-term PM2.5 exposure can initiate a sustained, post-exposure development of pulmonary fibrosis.
- The fibrosis progression is mediated by an oxidative-stress-initiated pathway involving NF-κB, inflammation, and EMT.
